Postnatal Probiotics and Allergic Disease in Very Preterm Infants: Sub-study to the ProPrems Randomized Trial

Probiotic supplementation to mothers and/or their term-born infants has been suggested to prevent development of allergic disease, particularly eczema. The goal of this study was to evaluate the impact of a postnatal probiotic combination on development of allergic diseases in very preterm infants.

ProPrems randomized 1099 very preterm infants, born <32 weeks' gestation and <1500 g, to receive a probiotic combination (Bifidobacterium infantis, Bifidobacterium lactis and Streptococcus thermophilus) or placebo from soon after birth until discharge from hospital or 40 weeks term corrected age (CA), whichever was earlier.

This substudy was an a priori secondary outcome of the ProPrems multi-center, double-blind, placebo-controlled randomized trial. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a sub-group of ProPrems infants (n = 281) as close to 12 months’ CA as possible by questionnaire, clinical exam, and skin prick tests to common allergens. Eczema was defined as history of itchy skin plus 3 or more of: visible dermatitis on extremities and/or cheeks; history of such skin findings; history of generally dry skin; and history of asthma or allergic rhinitis (or history of atopic disease in first degree relative). Atopic eczema was defined as eczema plus at least one positive skin prick test. Food allergy was defined as parent report of doctor-diagnosed allergy to cow milk, soy, egg, wheat or peanut. Wheeze was defined as any parent-reported wheeze. Skin prick testing was performed for egg white, cow milk, peanut, cat, rye grass pollen, and house dust mite.

Study participants ranged in age from 8–25 months; 84% were examined, and 82% underwent skin testing. Risk factors for allergy were similar in both groups. There was no difference in probiotic and placebo groups for any outcome measure: eczema 30% vs 27%; atopic eczema 5% vs 2%; food allergy 3% vs 1%; wheeze 31% vs 29%; and atopic sensitization 13% vs 11%.

There was no significant effect of postnatal probiotic supplementation on the incidence of eczema, atopic eczema, food allergy, wheeze, or atopic sensitization in this group of very preterm infants. However, the study was powered to detect a 15% reduction in incidence, and smaller magnitudes of effect cannot be excluded.

The authors point out that the World Allergy Organization–based Guidelines for Allergic Disease Prevention recommend probiotic use in pregnancy and the postnatal period for infants at increased risk of developing allergy but do not single out the specific circumstance of prematurity. The authors also emphasize that probiotic effects are dose, disease, and strain specific. Despite their apparent safety, it is hard to imagine that any probiotic regimen would have more than a very modest impact on overall atopic disease development, and likely be limited to transient eczema, if that.